Outcomes measurement is an important component of routine hemophilia care, clinical trials and economic evaluations. Assessing outcomes in patients living with hemophilia is challenging due to a lack of validated outcome measures. Conventional clinical outcomes, for instance, bleeding rate, structural changes of joints or functional joint scores may be less relevant for the decision-making process. Patient reported outcomes measures has been increasingly interested in routine medical care and clinical research. However, the available validated patients reported outcome measures for patients with hemophilia are not generally implemented in routine care or clinical trials. The Patent Reported Outcomes, Burdens, and Experiences (PROBE) study aims to develop a validated patient reported outcome measure for patients living with hemophilia. The PROBE questionnaire is organized in 4 sections, comprising 29 questions. Section I contains questions pertaining to demographic data. Section II contains questions pertaining to patient reported outcomes. Section III contains questions pertaining to hemophilia specific problems and treatments. Section IV contains the EuroQol five dimension 5-level instrument (EQ-5D-5L). The psychometric analysis of revealed that the PROBE questionnaire has a good internal consistency (Cronbach’s alpha coefficient=0.84). PROBE items showed moderate to strong correlations with corresponding EQ-5D-5L domains. The PROBE Score has a known group validity among known groups. The psychometric properties of the PROBE questionnaire demonstrated the validity of the instrument in both patients living with hemophilia and control population (participants without bleeding disorder). The test-retest reliability analysis demonstrated that the PROBE questionnaire has a substantial agreement when the questionnaire was repeatedly administrated. There were acceptable reliability properties between the paper-based and web-based questionnaires. The reliability properties of the PROBE questionnaire were established in both patients living with hemophilia and control population. The PROBE questionnaire was cross-cultural implemented in 21 countries. The results showed that the regions of participant contributed a trivial variability of the PROBE score, indicating that the PROBE questionnaire is valid for assessing the health status among hemophilia patients and participants without bleeding disorder across regions. Sexual health of patients living with hemophilia was evaluated using the PROBE questionnaire. The results showed that sexual difficulty was more prevalent in patients with hemophilia and associated with markers of disease severity. This finding warrants the sexual health assessment in routine hemophilia care. / Thesis / Doctor of Philosophy (PhD)

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Objective and Hypothesis The goals of this study are to address the following questions regarding shoulder arthroplasty (TSA): (a) Does restoring range of motion (ROM) lead to increased patient satisfaction? (b) How is ability to carry out activities of daily living (ADLs) influenced by ROM? (c) How does ADL performance correlate with patient satisfaction? We hypothesize that more “normal” ROM following TSA leads to increased patient satisfaction and better performance of ADLs. Methods Patients who underwent TSA, reverse TSA, hemiarthroplasty, or humeral head resurfacing were prospectively enrolled in a shoulder arthroplasty registry. 155 patients who had preoperative and 6 month postoperative data for ROM, patient satisfaction, and performance of ADLs were included in the study. Results Of these 155 shoulders, the response rate for patient satisfaction was only 82 (52.9%), with 96.8% reporting they were “satisfied or “very satisfied”. Postoperative ROM was associated with patient satisfaction for forward flexion, adduction, and external rotation. This association demonstrated a “dose;response” relationship, as higher percentage of normal ROM correlated with higher satisfaction. Mean ADL scores were higher for patients who achieved normal ROM in each plane of motion. The greatest improvement in mean ADL score occurred when a patient achieved normal ROM for at least 3 of 5 measurements. There was also a significant association between improved ADL and higher patient satisfaction. Significance Glenohumeral arthrosis causes considerable morbidity, and rates of shoulder arthroplasty are increasing. As the predominant goals of TSA are pain relief and restoration of ROM, it is important to assess postoperative patient satisfaction. While most historic studies have focused on measures of implant performance, interest is increasing in patient-centered outcomes. Both objective and subjective outcomes should be included in future large multicenter registries. Data collected from these registries has the potential to substantially improve success rates and longevity of shoulder arthroplasty.

Objective: Patient-reported outcomes (PROs) are measures collected from a patient to determine how he/she feels or functions in regards to a health condition. Longitudinal PROs, which are collected at multiple occasions from the same individual, may be affected by response shift (RS). RS is a change in a person’s self-evaluation of a target construct. Latent variable models (LVMs) are statistical models that relate observed variables to latent variables (LV). LVMs are used to analyze PROs and detect RS. LVs are random variables whose realizations are not observable. Factor scores are estimates of LVs for each individual and can be estimated from parameter estimates of LVMs. Factor scoring methods to estimate factor scores include: Thurstone, Bartlett, and sum scores. This simulation study examines the effects of RS on factor scores used to test for change in the LV means and recommend a factor scoring method least affected by RS. Methods: Data from two time points were fit to three confirmatory factor analysis (CFA) models. CFA models are a type of LVM. Each CFA model had different sets of parameters that were invariant over time. The unconstrained (Uncon) CFA model had no invariant parameters, the constrained (Con) model had all the parameters invariant, and the partially constrained (Pcon) model had some of the parameters invariant over time. Factor scores were estimated and tested for change over time via paired t-test. The Type I error, power, and factor loading (the regression coefficient between an observed and LV) and factor score bias were estimated to determine if RS influenced the test of change over time and factor score estimation. Results: The results depended on the true LV mean. The Type I error and power were similar for all factor scoring methods and CFA models when the LV mean was 0 at time 1. For LV mean of 0.5 at time 1 the Type I error and power increased as RS increased for all factor scores except for scores estimated from the Uncon model and Bartlett method. The biases of the factor loadings were unaffected by RS when estimated from an Uncon model. The factor scores estimated from the Uncon model and the Bartlett and sum scores method had the smallest factor score biases. Conclusion: The factor scores estimated from the Uncon model and the Bartlett method was least affected by RS and performed best in all measures of Type I error, statistical power, factor loading and factor score bias. Estimating factor scores from PROs data that ignores RS may result in erroneous (or biased) estimates.

Class of 2013 Abstract / Specific Aims: To assess the effect of a pharmacist-led education group on psychiatric patient-reported attitudes, knowledge, and confidence in self-managing medications. The reliability and validity of the questionnaire given to patients who attended a pharmacist-led medication education group was also evaluated. Methods: A retrospective pre-post questionnaire was distributed patients and collected variables collected including patient self-reported medication knowledge and attitudes, demographics, previous psychiatric hospitalizations, length of group attended, and outpatient pharmacist relationships. Knowledge and attitude items were measured on a 4-point Likert-type scale with response options ranging from “agree” to “disagree.” Rasch analysis was conducted to ensure all items measured the same construct and the probability of the person responding to an item was not dependent on other assessment items. Rasch measurement includes several diagnostic indices that allow item-specific and person-specific examinations of data reliability and measurement fit. In addition, the Rasch technique makes it possible to evaluate the contribution of each person’s measures on each item. A z-test was used to evaluate for instrument content gaps and a dependent t-test was performed to measure for statistical differences before and after the intervention. Main Results: Sixty patients responded to the Medication Attitude and Knowledge Questionnaire over a 16-week period. Gaps identified were not statistically significant (p=0.1064 and 0.5305) indicating that content validity is comprehensive. On a group level, no significant differences were identified in patient answers before and after the intervention (p=0.2162, p=0.8292). When each patient was analyzed separately, only one patient out of 60 showed a significant difference in answers after the intervention. Results also demonstrated that after attending a group, 100% of patients indicated they intended to adhere to their medication regimen post-discharge. Conclusion: This evaluation was unique because patient attitudes were explored before and after medication education group attendance. Medication Attitude and Knowledge items were valid and reliable.

Patient-reported outcome measures (PROMs) are becoming an integral part of healthcare decision making. Clinical trials, systematic reviews, and clinical practice guidelines incorporate them to learn about the effect of medical interventions in patients’ health status, without interference or mediation from clinicians or proxies. The use of these types of measures, however, is not without challenges. In particular, the complexity of the PROMs makes it difficult for patients, clinicians, and researchers to fully grasp the extent to which a treatment effect is negligible or trivial, small but important, moderate, or large. One of the most documented ways to address this issue is the use of the minimal important difference (MID), the smallest change in a PROM, either beneficial or harmful, that patients would perceive as important. A patient-oriented way to determine this threshold is the estimation of an anchor-based MID, where PROM results are compared against an external independent criterion the anchor that is in itself understandable and relevant for patients. This dissertation is an effort to facilitate the identification, evaluation, and utilization of MID estimates for PROMs. First, this thesis describes the development and reliability assessment of a new instrument to determine the credibility of primary studies ascertaining MID estimates, Second, it describes the conduct of a systematic survey to inform the creation of an inventory of all available anchor-based MIDs in the medical literature until 2015. Third, it reports an analysis of the state of the art of current MID estimates from a reporting and credibility perspective. Finally, this work concludes with a summary of the main results, presentation of strengths and limitations, and insights related to the implications for future research. / Dissertation / Doctor of Philosophy (PhD)

Background: Patient experience has become an essential quality indicator in healthcare. Purpose: The purpose of this thesis was to conduct a concept analysis of the patient experience. Methods: Walker and Avant’s methodology served as the framework for this concept analysis. Data were retrieved from seven databases and one search engine. The literature search used keywords related to "patient experience" and included articles published at any time up until March 2018. A total of 257 articles and organizational websites were included in the analysis after meeting the inclusion criteria. Results: Twenty attributes were found to define the patient experience: communication, respect for patients, information/education, patient-centered care, comfort/pain, discharge from hospital, hospital environment, professionalism/trust, clinical care/staff competency, access to care, global ratings, medication, transitions/continuity, emotional dimension, outcomes, hospital processes, safety/security, interdisciplinary team, social dimension, and patient dependent features. Conclusion: The results of this study will guide and clarify the critical concepts towards an explicit definition of the patient experience.

BACKGROUND. The study of patient reported outcomes (PROs) has seen an exponential increase in recent years. In order to be useful in practice, PRO questionnaires should be evaluated for validity, reliability, and responsiveness. Responsiveness, which assesses a questionnaire’s ability to capture changes in quality of life (QOL) when they occur, has not formally been evaluated in hemophilia-specific questionnaires. PRIMARY OBJECTIVE. To evaluate the responsiveness of the Patient Reported Outcomes, Burdens, and Experiences (PROBE) questionnaire in individuals living with hemophilia A or B following events of interest. SECONDARY OBJECTIVES. To evaluate the responsiveness of PROBE over periods in which no events occur. To explore the use of regression analysis in aiding interpretability. To assess the presence of response shift in the study population. METHODS. Participants will be asked to complete PROBE, as well as questions indicating changes in QOL, following a bleed or surgical intervention, and every 6 months. Responses will be evaluated using anchor-based and distribution-based approaches. OUTCOMES. Minimally important differences (MIDs) and minimally detectable changes (MDCs) will be calculated, graphically represented, and compared to determine a single or small range of MID values. STUDY IMPLICATIONS. Understanding responsiveness will provide increased interpretability of PROBE scores. Using an MID value, one can be confident that a change in PROBE score greater than the MID is beyond measurement error and indicates a change in QOL. This will allow for the use of PROBE in future research trials of drug effectiveness and can offer patients’ perspectives on their changes in QOL when switching to novel therapies. In addition, physicians may be able to use PROBE as a method of tracking and better understanding changes in their patients’ health statuses in the clinical setting. / Thesis / Master of Science (MSc) / This project hopes to identify the responsiveness of the Patient Reported Outcomes, Burdens, and Experiences (PROBE) Questionnaire. The responsiveness of a questionnaire is its ability to detect a change in health status when one has occurred. In order to measure whether PROBE can detect these changes, participants living with hemophilia A or B will be asked to fill out the questionnaire, as well as a few questions aimed at determining if their quality of life has changed, after they have a bleed or a surgery, as well as after 6 months. Collecting this information will help us understand how much the PROBE score needs to change in order for patients to consider a small but important change in health to have occurred. This will help with interpreting the PROBE score, which could then be used in research or in hemophilia clinics across Canada.

Osteoarthritis (OA) is one of the leading causes of global disability. Surgical intervention in the form of Total Knee Arthroplasty (TKA) has been established as an excellent treatment modality for people with OA who experience joint symptoms that have a substantial impact on their quality of life and are refractory to non-surgical treatment. In the 1970s the concept of implanting TKAs in mechanical alignment (MA) was developed as a compromise to confer mechanical advantage to the prosthesis, ignoring the patient's natural anatomy, to prevent early failure of the implant. Until now, this compromise has not been revisited. Satisfaction following TKA remains inferior to total hip arthroplasty. The cause of this dissatisfaction is not clear. Implant survival is no longer comparable to that of the early designs of TKA, and recent studies have suggested that deviation from neutral alignment does not have the detrimental effect on survivorship as previously thought. In an attempt to improve patient satisfaction following TKA a new technique has been developed whereby the prostheses are implanted in such a way as to recreate the alignment of the knee in the patient's pre-arthritic state. This has been termed natural or kinematic alignment (KA). This thesis examines the impact of KA in TKA with the primary hypothesis that TKA performed utilising KA would lead to improved functional outcome following surgery compared to that of MA. An initial single surgeon proof of concept case series of 25 patients was performed to look at the precision of new patient specific cutting blocks. The results suggested that the cutting blocks were accurate in producing the desired cuts. Following the proof of concept case series, a feasibility study was then performed comparing the new KA technique with the standard MA technique. The feasibility study familiarised the operating surgeons with the new technology in preparation for a Randomised Control Trial (RCT). A prospective blinded RCT was performed to compare the functional outcome of patients implanted with TKA in MA with that of KA. A total of 71 patients undergoing TKA were randomised to either MA (n=35) or KA (n=36). Preand post-operative hip knee ankle (HKA) radiographs were analysed. A number of patient reported outcome measures and functional tests were assessed pre-operatively, 6 weeks, 3 months, 6 months, and at 1 year post-operation. The cutting guides were accurate. There were no statistically significant differences between the MA and KA groups at 1 year. A cohort of post-menopausal women with unilateral osteoarthritis treated with TKA utilising the KA philosophy had dual energy x-ray absorptiometry scans 1.5 years post-operatively using a modified validated densitometric analysis protocol, to assess peri-prosthetic Bone Mineral Density (BMD). The contralateral knee was scanned so that relative bone mineral density could be calculated. Statistical analysis revealed no significant difference in relative peri-prosthetic bone mineral density due to variation in implant position with respect to the Lateral Distal Femoral Angle (LDFA) and the Medial Proximal Tibial Angle (MPTA). There was a significant correlation with overall HKA angle and the relative BMD under the medial side of the tibial tray. KA TKAs appear to have comparable short-term results to MA TKAs with no significant differences in function 1 year post-operatively. Overall HKA angle rather than the individual component position caused change in relative BMD under the tibial tray, therefore aiming for an anatomical joint line may improve kinematics without a detrimental effect on the implant. Further research is required to see if any theoretical long-term functional benefits of KA are realised or if there are any potential effects on implant survival.

Background: Commonly used response scales in patient-reported outcome (PRO) measures include the visual analogue scale, 11-point numeric rating scale, 5-point numeric rating scale, 5-point verbal rating scale, and 5-point verbal-numeric rating scale. Although prior studies have explored the interpretation of response scale labels and compared scores resulting from the response scale, many questions remain. Purpose: To identify sets of verbal descriptors interpreted with the least variation and to explore whether the response scales provide interval level data and whether the scales are interchangeable. Methods: Subject recruitment and screening was through an online drug-drug interaction service (MediGuard.org). Via an online survey platform, subjects used a scale (0 = lowest possible and 10=highest possible) to assign interpretation scores to verbal descriptors. Repeated measures analysis of variance informed the test interval data between scores. Subjects also completed repeated administrations of four symptom-specific item stems with different response scales. Ordinal regression informed the analysis of scores assigned to verbal descriptors, comparison of probabilities of responding in given categories across scales, and prediction of response category on one scale conditional on observed response on another scale. Cut-points informed tests for interval level data. Results: The sample (n=350) comprised 223 females and 127 males with a mean (SD) age of 56.9 (12.1) years. Number of health conditions per subject ranged from 1 to 12 (median = 5). Age, sex, level of education, and number of health conditions were associated with the interpretation of verbal descriptors. Scores assigned to "poor," "fair," "good," "very good," "excellent," "somewhat," "sometimes," and "quite a bit," had the largest variation. The probability of responding in the same categories on the different response scales was significantly different across scales before and after collapsing categories. No scale yielded interval level data. The 11-NRS data tended more towards interval level than the data from other scales. Conclusions: Using different response scales with verbal descriptors in non-randomized studies may introduce bias. Differential item functioning and subgroup analyses should be investigated in the development and use of these response scales. The scales are not interchangeable. Compared with other scales the 11-NRS produced data approaching interval level. Collapsing categories entails significant probabilities of misclassification.

Electronic data capture technologies, such as interactive voice response (IVR) systems, are emerging as important alternatives for collecting self-reported data. The purpose of this research was to assess the measurement equivalence between the original paper-based versions and the adapted interactive voice response (IVR) versions of the EQ-5D and the QLQ-C30. Furthermore, we examined the test-retest reliability of two consecutive administrations of the IVR versions of the EQ-5D and the QLQ-C30. The comparison of the paper and IVR versions of the EQ-5D was conducted utilizing a crossover design with subjects randomly assigned to one of two assessment orders: 1) paper then IVR or 2) IVR then paper. A convenience sample of in-treatment outpatient cancer clinic patients (n=139) were asked to complete each assessment two days apart. For the test-retest component, outpatient cancer clinic patients (n=127) were asked to complete the IVR-based EQ-5D twice, two days apart. The analyses tested for mean differences (paired t-test) and test-retest reliability (ICC).In the crossover analysis, ten of the fifteen mean differences analyzed for the scales and items of the QLQ-C30 were within the equivalence interval set a priori. The ICCs for the scales and items of the QLQ-C30 ranged from 0.698 to 0.899. Two of the items, insomnia and appetite loss, did not meet our threshold of being statistically different from an ICC of 0.70. The EQ-5D index score means were equivalent between paper and IVR, however the EQ VAS score differences were not wholly contained in the equivalence interval. The ICCs were above 0.890 for the index and the EQ VAS. In the test-retest analysis, the ICCs for the nine multi-item scales for the QLQ-C30 were all above 0.69, ranging from 0.698 to 0.891. Ten of the fifteen mean differences analyzed were within the equivalence interval set a priori. For the EQ-5D, the mean differences were wholly contained within the equivalence intervals for both the index and the EQ VAS and the ICCs were significantly different from 0.70. Overall, the IVR version of the questionnaires provided psychometrically equivalent results to those obtained on the original paper version and showed good stability over time.